Examining the New Consensus Criteria for Traumatic Encephalopathy Syndrome in Community-Dwelling Older Adults.

In 2021, an expert panel of clinician-scientists published the first consensus research diagnostic criteria for traumatic encephalopathy syndrome (TES), a clinical condition thought to be associated with chronic traumatic encephalopathy neuropathological change. This study evaluated the TES criteria in older adults and assessed associations between TES criteria and a history of repetitive head impacts. This cross-sectional, survey-based study examined the symptoms of TES, previous repetitive head impacts, and a variety of current health difficulties. To meet symptom criteria for TES, participants had to report progressive changes with memory, executive functioning, and/or neurobehavioral dysregulation. To meet the criterion for substantial exposure to repetitive head impacts via contact sports, participants reported at least 5 years of contact sport exposure (with 2+ years in high school or beyond). A sample of 507 older adults (mean age = 70.0 years, 65% women) completed the survey and 26.2% endorsed having one or more of the progressive core clinical features of TES. Those who had a significant history of contact sport exposure were not significantly more likely to meet TES criteria compared with those who did not (31.3% vs. 25.3%, p = 0.46). In a binary logistic regression predicting TES status, current depression or anxiety (odds ratio [OR] = 12.55; 95% confidence interval [CI] = 4.43-35.51), history of psychiatric disorders (OR = 2.07, 95% CI = 1.22-3.49), male sex (OR = 1.87), and sleep problems (OR = 1.71, 95% CI = 1.01-2.91) were associated with meeting TES criteria. The sport exposure criterion, age, and current pain were not significantly associated with TES status (ps > 0.05). A significant minority of participants with no history of neurotrauma endorsed symptoms consistent with TES (22.0% of men and 19.8% of women). Nearly 80% of neurotrauma naïve participants with clinically significant anxiety/depression met criteria for TES. In summary, approximately one in four older adults met the symptom criteria for TES, many of whom had no history of repetitive neurotrauma. Mental health problems and sleep issues were associated with TES, whereas having a history of repetitive head impacts in contact sports was not. These data suggest that the new consensus diagnostic criteria for TES may have low specificity and may carry a higher risk of misdiagnosing those with other physical and mental health conditions as having TES.

A systematic review on the risk of neurodegenerative diseases and neurocognitive disorders in professional and varsity athletes.

OBJECTIVE: The aim of this systematic review (SR) was to gather all available epidemiological evidence on former participation in any type of sport, at a professional and varsity level, as a potential risk factor for neurodegenerative diseases (NDs) and neurocognitive disorders (NCDs). DESIGN: Systematic searches were performed on PubMed, the Cochrane databases, and the ISI Web of Knowledge databases. Included studies were assessed using the NOS checklist. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: All epidemiological studies reporting data on the possible association between a clinical diagnosis of amyotrophic lateral sclerosis (ALS)/motor neuron disease (MND), dementia or mild cognitive impairment (MCI), Parkinson's disease (PD), chronic traumatic encephalopathy (CTE) at any stage and with any clinical pattern and the former participation in any types of sport at a varsity and professional level were included. RESULTS: Data from the 17 included studies showed a higher frequency of NDs and NCDs in former soccer and American football players. Updating the previous SR confirmed a higher frequency of ALS/MND in former soccer players. Data reported a significantly higher risk of dementia/AD in former soccer players, and of MCI in former American football players. Results also showed a significantly higher risk of PD in former soccer and American football players, and a significantly higher risk of CTE in former boxers and American football players. This SR confirmed a higher risk of NDs and NCDs in former professional/varsity athletes. However, the pathological mechanisms underlying this association remain unclear, and further high-quality studies should be performed to clarify whether the association could be sport specific.

The burden of unsubstantiated messaging: collegiate athletes' chronic traumatic encephalopathy mechanism beliefs.

OBJECTIVE: To investigate factors associated with collegiate athletes' beliefs regarding chronic traumatic encephalopathy (CTE) mechanism. DESIGN: Cross-sectional study. METHODS: A total of 838 collegiate athletes (61.9% men) from seven institutions completed a 10-minute survey that captured information relative to demographics, diagnosed concussion history, formal sport-related concussion education, additional sources of concussion information, and beliefs about multiple concussions and premature return-to-play following a head impact as mechanisms for CTE. RESULTS: More than half of collegiate athletes believed that multiple concussions (58.2%) and premature return-to-play (59.1%) may cause CTE. Those who reported getting concussion information from sports news had higher odds of believing multiple concussions and premature return-to-play were CTE mechanisms compared to those who did not get information from sports news sources. Additionally, CTE mechanism beliefs were significantly greater in collegiate athletes who were male, had sustained a previous diagnosed concussion, or had acquired concussion information from the NCAA. CONCLUSIONS: Sports news' reporting of CTE storylines, which highlight former male athletes with complex brain injury histories, may influence collegiate athletes' beliefs about concussion. Therefore, it is recommended that concussion awareness initiatives incorporate information related specifically to CTE to empower collegiate athletes with evidence-based, patient-oriented information and knowledge regarding this condition.

Identifying degenerative effects of repetitive head trauma with neuroimaging: a clinically-oriented review.

BACKGROUND AND SCOPE OF REVIEW: Varying severities and frequencies of head trauma may result in dynamic acute and chronic pathophysiologic responses in the brain. Heightened attention to long-term effects of head trauma, particularly repetitive head trauma, has sparked recent efforts to identify neuroimaging biomarkers of underlying disease processes. Imaging modalities like structural magnetic resonance imaging (MRI) and positron emission tomography (PET) are the most clinically applicable given their use in neurodegenerative disease diagnosis and differentiation. In recent years, researchers have targeted repetitive head trauma cohorts in hopes of identifying in vivo biomarkers for underlying biologic changes that might ultimately improve diagnosis of chronic traumatic encephalopathy (CTE) in living persons. These populations most often include collision sport athletes (e.g., American football, boxing) and military veterans with repetitive low-level blast exposure. We provide a clinically-oriented review of neuroimaging data from repetitive head trauma cohorts based on structural MRI, FDG-PET, Aß-PET, and tau-PET. We supplement the review with two patient reports of neuropathology-confirmed, clinically impaired adults with prior repetitive head trauma who underwent structural MRI, FDG-PET, Aß-PET, and tau-PET in addition to comprehensive clinical examinations before death. REVIEW CONCLUSIONS: Group-level comparisons to controls without known head trauma have revealed inconsistent regional volume differences, with possible propensity for medial temporal, limbic, and subcortical (thalamus, corpus callosum) structures. Greater frequency and severity (i.e., length) of cavum septum pellucidum (CSP) is observed in repetitive head trauma cohorts compared to unexposed controls. It remains unclear whether CSP predicts a particular neurodegenerative process, but CSP presence should increase suspicion that clinical impairment is at least partly attributable to the individual's head trauma exposure (regardless of underlying disease). PET imaging similarly has not revealed a prototypical metabolic or molecular pattern associated with repetitive head trauma or predictive of CTE based on the most widely studied radiotracers. Given the range of clinical syndromes and neurodegenerative pathologies observed in a subset of adults with prior repetitive head trauma, structural MRI and PET imaging may still be useful for differential diagnosis (e.g., assessing suspected Alzheimer's disease).

Chronic Traumatic Encephalopathy and Neuropathological Comorbidities.

With age, the presence of multiple neuropathologies in a single individual becomes increasingly common. Given that traumatic brain injury and the repetitive head impacts (RHIs) that occur in contact sports have been associated with the development of many neurodegenerative diseases, including chronic traumatic encephalopathy (CTE), Alzheimer's disease, Lewy body disease, and amyotrophic lateral sclerosis, it is becoming critical to understand the relationship and interactions between these pathologies. In fact, comorbid pathology is common in CTE and likely influenced by both age and the severity and type of exposure to RHI as well as underlying genetic predisposition. Here, we review the major comorbid pathologies seen with CTE and in former contact sports athletes and discuss what is known about the associations between RHI, age, and the development of neuropathologies. In addition, we examine the distinction between CTE and age-related pathology including primary age-related tauopathy and age-related tau astrogliopathy.

Advances in chronic traumatic encephalopathy.

Over the past decade, concern for negative outcomes associated with concussive brain trauma has grown immensely. These neuropathologic changes, termed chronic traumatic encephalopathy (CTE), have been linked to patients who exhibit neuropsychiatric symptoms and have experienced repetitive brain trauma. Recent publicity has brought about renewed interest in this progressive neurodegenerative disorder. This article will share the advances that have been made with CTE.

Chronic traumatic encephalopathy research viewed in the public domain: What makes headlines?

Objective: To determine chronic traumatic encephalopathy (CTE)-related publication characteristics associated with higher Altmetric scores.Methods: A systematic review of the CTE literature was conducted using PubMed. Publications were coded for: journal impact factor (JIF); publication type (primary versus non-primary data collection); discussion of American football; contact sport-CTE association conclusion (yes versus no/neutral); and Altmetric score. Multivariable ordinal logistic regression identified predictors of higher Altmetric scores.Results: Most of the 270 CTE-related publications did not include primary data collection (60%). The median Altmetric score was 12 (range = 0-3745). Higher Altmetric scores were associated with primary data collection [Odds ratio (OR)Adjusted = 2.29; 95% confidence interval (CI) = 1.35-3.89] and discussing American football (ORAdjusted = 2.11; 95%CI = 1.24-3.59). Among publications concluding contact sport-CTE associations, higher Altmetric scores were associated with higher JIF (3-point-JIF-increase ORAdjusted = 2.11; 95%CI = 1.24-3.59); however, the association of higher Altmetric scores with higher JIF was not found among neutral publications or those concluding no contact sport-CTE associations (3-point-JIF-increase ORAdjusted = 1.07; 95%CI = 0.94-1.22).Conclusions: Most CTE-related publications (60%) did not involve primary data collection. Publication characteristics such as higher JIF and concluding contact sport-CTE associations were associated with higher Altmetric scores. It is important for the academic community to consider strategies to counter publication and promotion bias in the presentation of CTE literature.

Risk of Misdiagnosing Chronic Traumatic Encephalopathy in Men With Depression.

OBJECTIVE: In recent years, it has been proposed that depression represents one clinical subtype of chronic traumatic encephalopathy (CTE). This is the first study to examine the specificity of the research criteria for the clinical diagnosis of CTE in men with depression from the general population. METHODS: Data from the National Comorbidity Survey Replication, an in-person survey that examined the prevalence and correlates of mental disorders in the United States, were used for this study. Men diagnosed as having a major depressive episode in the past 30 days were included (N=101; mean age=39.4 years, SD=12.9, range=18-71). They were deemed to meet research criteriafor CTE if they presented with the purported supportive clinical features of CTE (e.g., impulsivity and substance abuse, anxiety, apathy, suicidality, and headache). RESULTS: Approximately half of the sample (52.5%) met the proposed research criteria for CTE (i.e., traumatic encephalopathy syndrome). If one accepts the delayed-onset criterion as being present, meaning that the men in the sample were presenting with depression years after retirement from sports or the military, then 83.2% of this sample would meet the research criteria for diagnosis. CONCLUSIONS: The clinical problems attributed to CTE, such as depression, suicidality, anxiety, anger control problems, and headaches, co-occurred in this sample of men with depression from the general population-illustrating that these problems are not specific or unique to CTE. More research is needed to determine whether depression is, in fact, a clinical subtype of CTE.

A model for intervening with veterans and service members who are concerned about developing Chronic Traumatic Encephalopathy (CTE).

OBJECTIVE: This paper briefly reviews what is unknown about chronic traumatic encephalopathy (CTE), highlights understandable concerns by individuals with a history of mild traumatic brain injuries who present to neuropsychologists with fears about a deteriorating course and eventual dementia due to CTE, and proposes a three-phased model for intervening with such individuals. METHOD: The proposed model includes three phases - (1) assessment and education, (2) targeted interventions for specific symptoms and comorbidities (e.g., sleep disturbance, headache, depression), and (3) psychotherapy to address mental health issues. While this is generally the order in which they will occur, the approach is not necessarily linear but rather provides a recommended schema. CONCLUSION: Media attention on concussion has greatly increased in the last several years, as interest in the possible contribution of concussion(s) to CTE grows. This media attention has some adverse effects in that it creates a false perception about the current state of the science and may engender iatrogenic effects. The proposed model is offered as one approach to engage patients within this context.

Tau pathology in the medial temporal lobe of athletes with chronic traumatic encephalopathy: a chronic effects of neurotrauma consortium study.

Chronic traumatic encephalopathy (CTE) is a progressive neurodegenerative condition associated with repetitive traumatic brain injury (rTBI) seen in contact-sport athletes and military personnel. The medial temporal lobe (MTL; i.e., hippocampus, subiculum, and entorhinal and perirhinal cortices) memory circuit displays tau lesions during the pathological progression of CTE. We examined MTL tissue obtained from 40 male Caucasian and African American athletes who received a postmortem CTE neuropathological diagnosis defined as stage II, III, or IV. Sections were immunolabeled using an early (AT8) or a late (TauC3) marker for pathological tau and for amyloid beta (Aß) species (6E10, Aß1-42 and thioflavin S). Stereological analysis revealed that stage III had significantly less AT8-positive neurons and dystrophic neurites than stage IV in all MTL regions except hippocampal subfield CA3, whereas significantly more AT8-positive neurons, dystrophic neurites, and neurite clusters were found in the perirhinal cortex, entorhinal cortex, hippocampal CA1, and subiculum of CTE stage III compared with stage II. TauC3-positive pathology was significantly higher in the perirhinal and subicular cortex of stage IV compared to stage III and the perirhinal cortex of stage III compared to stage II. AT8-positive neurite clusters were observed in stages III and IV, but virtually absent in stage II. When observed, Aß pathology appeared as amyloid precursor protein (APP)/Aß (6E10)-positive diffuse plaques independent of region. Thioflavine S labeling, did not reveal evidence for fibril or neuritic pathology associated with plaques, confirming a diffuse, non-cored plaque phenotype in CTE. Total number of AT8-positive profiles correlated with age at death, age at symptom onset, and time from retirement to death. There was no association between AT8-positive tau pathology and age sport began, years played, or retirement age, and no difference between CTE stage and the highest level of sport played. In summary, our findings demonstrate different tau profiles in the MTL across CTE stages, proffering CA3 tau pathology and MTL dystrophic neurite clusters as possible markers for the transition between early (II) and late (III/IV) stages, while highlighting CTE as a progressive noncommunicative tauopathy.

Chronic Traumatic Encephalopathy (CTE) Is Absent From a European Community-Based Aging Cohort While Cortical Aging-Related Tau Astrogliopathy (ARTAG) Is Highly Prevalent.

This study determined the prevalence of chronic traumatic encephalopathy (CTE) and cortical aging-related tau astrogliopathy (ARTAG) in a European community-based population (n = 310). The frontal, parietal, and temporal cortices, representing initial stages of CTE were assessed. No case fulfilling CTE consensus criteria was found. However, isolated astroglial or neuronal tau pathologies were recognized in the depths of cortical sulci (<2%). A single case (female, 85 years) without a history of traumatic brain injury (TBI) showed combined tau-immunoreactive features confined to frontal sulci without perivascular accumulation. Another 24 cases had single tau pathologies in cortical sulci. ARTAG was identified in 117 cases (38%), with a similar regional prevalence. Gray matter ARTAG was the most common followed by subpial, white matter, and perivascular. The presence of any type of ARTAG was strongly associated with having another type of ARTAG in the same region (p < 0.05). In summary, although isolated tau pathologies in the depths of cortical sulci were identified, no case fulfilled diagnostic criteria of CTE. Cortical ARTAG in this population is common and contrasts the high prevalence of CTE in individuals with repeated mild TBI. ARTAG in isolation might not be indicative of CTE although commonalities in pathogenesis should be considered.

No Evidence of Increased Chronic Traumatic Encephalopathy Pathology or Neurodegenerative Proteinopathy in Former Military Service Members: A Preliminary Study.

It is presently unknown whether military service members are at risk for chronic traumatic encephalopathy (CTE) or Alzheimer's disease (AD) pathology, due to traumatic brain injury (TBI). Studies with respect to AD have had mixed results with respect to mild TBI, although an increased risk of clinical AD with moderate and severe TBI is more consistently demonstrated. No studies to date have demonstrated a longitudinal progression from TBI to autopsy. We therefore initiated a cross-sectional survey of former military service members. 18 brain specimens have been examined to date, with a mean age of 68.9±16 years (range 32-94). Twelve had a history of psychiatric problems; 10 had a history of PTSD specifically. Five had neurological problems including stroke and seizures. One subject had early-onset AD. Two subjects had a history of TBI and two had a history of blast exposure. Age-related proteinopathy, ranging from AD neuropathologic change A0B1C0 to A3B3C3 by NIA-AA guidelines, was identified. None of the cases showed changes specific for CTE pathology. There was no relationship between p-tau in the amygdala and psychiatric signs. There was no significant difference in phosphorylated tau (p-tau) or amyloid-ß burden compared to age-matched controls. These preliminary data suggest that military service per se is not a risk factor for CTE pathology or neurodegenerative proteinopathy. More research is needed to study the relationship, if any, between TBI and neurodegenerative proteinopathy.

Chronic Traumatic Encephalopathy Within an Amyotrophic Lateral Sclerosis Brain Bank Cohort.

Chronic traumatic encephalopathy (CTE) is a progressive neurodegenerative disorder linked to repetitive head impacts and has been associated with amyotrophic lateral sclerosis (ALS), a fatal, degenerative neuromuscular disorder. The Department of Veterans Affairs Biorepository Brain Bank (VABBB) is a tissue repository that collects antemortem disease progression data and postmortem central nervous system tissue from veterans with ALS. We set out to determine the frequency of co-morbid ALS and CTE in the VABBB cohort and to characterize the clinical, genetic, and pathological distinctions between participants with ALS only and those with both ALS and CTE (ALS+CTE). Of 155 participants, 9 (5.8%) had neuropathologically confirmed ALS+CTE. Participants with ALS+CTE were more likely to have a history of traumatic brain injury (p < 0.001), served during the first Persian Gulf War (p < 0.05), and to have more severe tau pathology within the frontal cortex and spinal cord (p < 0.05). The most common exposures to head impacts included contact sports (n = 5) and military service (n = 2). Clinically, participants with ALS+CTE were more likely to have bulbar onset ALS (p = 0.006), behavioral changes (p = 0.002), and/or mood changes (p < 0.001). Overall, compared with ALS in isolation, comorbid ALS+CTE is associated with a history of TBI and has a distinct clinical and pathological presentation.

Chronic traumatic encephalopathy: what do parents of youth athletes know about it?

INTRODUCTION/BACKGROUND: Chronic Traumatic Encephalopathy (CTE) is a neurodegenerative disease thought to be caused by repeated head impacts and associated with deficits in cognition. Despite research and media attention, there is little science-based information available for the public. Also unclear is what the public and particularly parents of youth athletes know about CTE. The U.S. Centers for Disease Control and Prevention (CDC) surveyed parents of young athletes to fill this gap. METHODS: CDC analysed 12 CTE-related questions that appeared in Porter Novelli Public Service's 2017 SummerStyles opinion survey. Analyses focused on 674 parents of children who play in a youth sports programme. RESULTS: Half of parents had at least one child who plays contact sports. About one-third of respondents reported being somewhat or very familiar with CTE. Most parents (81.7%) have not received educational materials on CTE from a school or sports programme. Healthcare providers were the preferred source of information about CTE (70%), followed by sports coaches (54%). DISCUSSION/CONCLUSION: This analysis identified information needs related to CTE among parents of young athletes. These findings can be used by health educators to tailor educational materials to meet information needs. Educational materials that emphasize potential prevention strategies and symptom onset may be beneficial.

Chronic Traumatic Encephalopathy and Neurodegeneration in Contact Sports and American Football.

Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease characterized by the presence of abnormally phosphorylated tau protein in the depths of one or more cortical sulci. Controversy over the risk of CTE and neurologic disorders later in life among contact sport athletes has taken hold in the public spotlight, most notably in American football. Players, parents, coaches, and legislators have taken action based on the commonly held notion that contact sports invariably lead to neurodegenerative disorders. However, to fully understand the science behind this assumed association, a critical appraisal of the evidence is warranted. With regards to CTE in sports, the objectives of the current report are to: 1) describe the history of CTE, 2) review current CTE definitions, 3) critically evaluate the empiric data, divided into all contact sports and exclusively American football, and 4) summarize notable themes for future research.

Assessing the Limitations and Biases in the Current Understanding of Chronic Traumatic Encephalopathy.

Chronic traumatic encephalopathy (CTE) is considered to be a progressive neurodegenerative disease caused by mild traumatic brain injury (mTBI). Recently there has been a significant amount of media attention surrounding the commonness of CTE in professional athletes, particularly American football, based on several postmortem case series. However, despite the persuasive claims made by the media about CTE, research on the disease and the effects of mTBI in general remain in its infancy. Commonly cited case series studying CTE are limited by methodological biases, pathological inconsistencies, insufficient clinical data, and a reliance on inherently biased postmortem data. These case series do not allow for the collection of any epidemiological data and are not representative of the general population. The exaggerated assumptions and assertions taken from these studies run the risk of creating a self-fulfilling prophecy for individuals who believe they are at risk and have the potential to negatively influence sports-related policymaking. This review outlines the status and limitations of recent CTE case series and calls for future prospective, longitudinal studies to further characterize the pathological and clinical hallmarks of CTE.

Research Gaps and Controversies in Chronic Traumatic Encephalopathy: A Review.

Importance: Scientific and lay interest in negative outcomes associated with exposure to repetitive brain trauma (RBT) continues to strengthen. Concerns about the association between RBT and dementia began more than a century ago, but have resurfaced in the last decade with the more recently described chronic traumatic encephalopathy (CTE). Chronic traumatic encephalopathy is a tauopathy associated with RBT that has become inextricably linked to conversations about sport-related concussion and mild traumatic brain injury. Accordingly, specific populations such as collision sport athletes and certain military personnel are of particular interest owing to their unique exposure to RBT. The gaps and controversies in our understanding of the epidemiologic factors, mechanism, and clinicopathological correlates of CTE reflect the current reliance on postmortem case series investigations. This review discusses the state of the science of CTE and raises considerations for researching and interpreting cognitive changes in members of at-risk populations. Observations: The recent development of pathological diagnostic criteria for CTE represented an important step for differentiating CTE from other neurodegenerative diseases. By comparison, defining the clinical syndrome(s) associated with CTE and the necessary and sufficient symptoms needed for its diagnosis lags behind. The absence of validated in vivo biomarkers of pathological characteristics of CTE and longitudinal tracking with neuropsychological evaluation remains a significant hurdle. Attribution of candidate symptoms in retired athletes to CTE is complicated by the presence of multiple premorbid and comorbid factors affecting cognitive reserve that influence normal or expected cognitive functioning. This is a critical issue in appropriately defining reference groups for normative comparisons. Conclusions and Relevance: Available data, while limited and complicated by selection bias, indicate that exposure to RBT represents the greatest risk factor for CTE pathological features, although clinicopathological correlates and the nature of onset and progression of symptoms are largely unknown. Considering aspects of cognitive reserve is likely essential for both interpreting cognitive outcomes associated with CTE and for developing preventive treatment programs. Research on CTE would benefit greatly from incorporating principles established within other areas of neurodegenerative disease and the nuances of clinicopathological considerations.

Head Trauma in Jail and Implications for Chronic Traumatic Encephalopathy in the United States: Case Report and Results of Injury Surveillance in NYC Jails.

Because there is no standard reporting of injuries in jails and prisons, the national burden of head trauma during incarceration is unclear. We report on a case of repeated head trauma in the New York City (NYC) jail system, data on the incidence of head trauma and mild traumatic brain injury (mTBI), and compare those findings with national estimates. The case report revealed 64 injurious events over two years, 44% resulting in a head injury and 25% resulting in emergency hospitalization. During the 42 months of this analysis, 10,286 incidents of head trauma occurred in the NYC jail system. Mild TBI occurred in 1,507 of these instances. The rate of head trauma and mTBI was 269.0 and 39.4 per 1,000 person-years, respectively. The lack of reporting head trauma in correctional settings means that national prevalence estimates of these critical health outcomes miss the vulnerable cohort of incarcerated individuals.

The multi-factorial origins of Chronic Traumatic Encephalopathy (CTE) symptomology in post-career athletes: The athlete post-career adjustment (AP-CA) model.

CTE has two prominent components: the pathophysiology that is detected in the brain postmortem and the symptomology that is present in the interval between retirement and end of life. CTE symptomology has been noted to include memory difficulties, aggression, depression, explosivity, and executive dysfunction at early stages progressing to problems with attention, mood swings, visuospatial difficulties, confusion, progressive dementia, and suicidality (e.g. McKee et al. (2012), Omalu et al. (2010a-c), McKee et al. (2009)). There are a number of assumptions embedded within the current CTE literature: The first is the assumption that CTE symptomology reported by athletes and their families is the product of the pathophysiology change detected post-mortem (e.g. McKee et al. (2009)). At present, there is little scientific evidence to suggest that all CTE symptomology is the product of CTE pathophysiology. It has been assumed that CTE pathophysiology causes CTE symptomology (Meehan et al. (2015), Iverson et al. (2016)) but this link has never been scientifically validated. The purpose of the present work is to provide a multi-factorial theoretical framework to account for the symptomology reported by some athletes who sustain neurotrauma during their careers that will lead to a more systematic approach to understanding post-career symptomology. There is significant overlap between the case reports of athletes with post-mortem diagnoses of CTE, and symptom profiles of those with a history of substance use, chronic pain, and athlete career transition stress. The athlete post-career adjustment (AP-CA) model is intended to explain some of the symptoms that athletes experience at the end of their careers or during retirement. The AP-CA model consists of four elements: neurotrauma, chronic pain, substance use, and career transition stress. Based on the existing literature, it is clear that any one of the four elements of the AP-CA model can account for a significant number of CTE symptoms. In addition, depression can be a chronic lifelong co-morbid condition that may be present prior to an athletic career, or may be developed secondary to any of the model elements as shown in Fig. 1. Notably, neurotrauma is a necessary, but not a sufficient condition, for the development of CTE symptomology.